CA2814018C - Preparation process of (6r)-tetrahydrobiopterin hydrochloride - Google Patents
Preparation process of (6r)-tetrahydrobiopterin hydrochloride Download PDFInfo
- Publication number
- CA2814018C CA2814018C CA2814018A CA2814018A CA2814018C CA 2814018 C CA2814018 C CA 2814018C CA 2814018 A CA2814018 A CA 2814018A CA 2814018 A CA2814018 A CA 2814018A CA 2814018 C CA2814018 C CA 2814018C
- Authority
- CA
- Canada
- Prior art keywords
- solvent
- hydrogenation
- tetrahydrobiopterin
- present
- hydrochloride
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- RKSUYBCOVNCALL-NTVURLEBSA-N sapropterin dihydrochloride Chemical compound Cl.Cl.N1=C(N)NC(=O)C2=C1NC[C@H]([C@@H](O)[C@@H](O)C)N2 RKSUYBCOVNCALL-NTVURLEBSA-N 0.000 title claims abstract description 26
- 238000002360 preparation method Methods 0.000 title claims abstract description 14
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims abstract description 51
- 229910000402 monopotassium phosphate Inorganic materials 0.000 claims abstract description 17
- 235000019796 monopotassium phosphate Nutrition 0.000 claims abstract description 17
- PJNZPQUBCPKICU-UHFFFAOYSA-N phosphoric acid;potassium Chemical compound [K].OP(O)(O)=O PJNZPQUBCPKICU-UHFFFAOYSA-N 0.000 claims abstract description 17
- 239000000758 substrate Substances 0.000 claims abstract description 11
- 239000002904 solvent Substances 0.000 claims description 43
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 37
- 238000000034 method Methods 0.000 claims description 35
- 239000000047 product Substances 0.000 claims description 32
- 230000008569 process Effects 0.000 claims description 30
- 239000003054 catalyst Substances 0.000 claims description 22
- LHQIJBMDNUYRAM-UHFFFAOYSA-N L-erythro-Biopterin Natural products N1=C(N)NC(=O)C2=NC(C(O)C(O)C)=CN=C21 LHQIJBMDNUYRAM-UHFFFAOYSA-N 0.000 claims description 21
- LHQIJBMDNUYRAM-DZSWIPIPSA-N L-erythro-biopterin Chemical compound N1=C(N)NC(=O)C2=NC([C@@H](O)[C@@H](O)C)=CN=C21 LHQIJBMDNUYRAM-DZSWIPIPSA-N 0.000 claims description 21
- 238000005984 hydrogenation reaction Methods 0.000 claims description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 17
- 238000004519 manufacturing process Methods 0.000 claims description 14
- 238000001953 recrystallisation Methods 0.000 claims description 12
- 238000001914 filtration Methods 0.000 claims description 11
- 229910052751 metal Inorganic materials 0.000 claims description 10
- 239000002184 metal Substances 0.000 claims description 10
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 9
- 239000000706 filtrate Substances 0.000 claims description 7
- 239000002253 acid Substances 0.000 claims description 6
- 230000000087 stabilizing effect Effects 0.000 claims description 5
- 150000001298 alcohols Chemical class 0.000 claims description 3
- 229910052739 hydrogen Inorganic materials 0.000 claims description 3
- 239000001257 hydrogen Substances 0.000 claims description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 32
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 16
- 239000013078 crystal Substances 0.000 description 15
- 239000000203 mixture Substances 0.000 description 15
- FNKQXYHWGSIFBK-RPDRRWSUSA-N sapropterin Chemical compound N1=C(N)NC(=O)C2=C1NC[C@H]([C@@H](O)[C@@H](O)C)N2 FNKQXYHWGSIFBK-RPDRRWSUSA-N 0.000 description 14
- 238000006243 chemical reaction Methods 0.000 description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 239000000243 solution Substances 0.000 description 9
- 239000011541 reaction mixture Substances 0.000 description 8
- YKIOKAURTKXMSB-UHFFFAOYSA-N adams's catalyst Chemical compound O=[Pt]=O YKIOKAURTKXMSB-UHFFFAOYSA-N 0.000 description 7
- 238000004821 distillation Methods 0.000 description 7
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
- 239000007864 aqueous solution Substances 0.000 description 6
- 239000007787 solid Substances 0.000 description 6
- 238000004128 high performance liquid chromatography Methods 0.000 description 5
- 150000007522 mineralic acids Chemical class 0.000 description 5
- 150000007524 organic acids Chemical class 0.000 description 5
- 230000020477 pH reduction Effects 0.000 description 5
- 150000003839 salts Chemical class 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 239000012265 solid product Substances 0.000 description 4
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 3
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 3
- 239000003513 alkali Substances 0.000 description 3
- 239000001530 fumaric acid Substances 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 239000011975 tartaric acid Substances 0.000 description 3
- 235000002906 tartaric acid Nutrition 0.000 description 3
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 3
- HNXQXTQTPAJEJL-UHFFFAOYSA-N 2-aminopteridin-4-ol Chemical compound C1=CN=C2NC(N)=NC(=O)C2=N1 HNXQXTQTPAJEJL-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- 239000005515 coenzyme Substances 0.000 description 2
- 239000012046 mixed solvent Substances 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 229910052697 platinum Inorganic materials 0.000 description 2
- 238000011085 pressure filtration Methods 0.000 description 2
- -1 primary Chemical class 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- 206010010904 Convulsion Diseases 0.000 description 1
- 206010033799 Paralysis Diseases 0.000 description 1
- 108010069013 Phenylalanine Hydroxylase Proteins 0.000 description 1
- 102100038223 Phenylalanine-4-hydroxylase Human genes 0.000 description 1
- 201000011252 Phenylketonuria Diseases 0.000 description 1
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000036461 convulsion Effects 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 239000002858 neurotransmitter agent Substances 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000011282 treatment Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D475/00—Heterocyclic compounds containing pteridine ring systems
- C07D475/02—Heterocyclic compounds containing pteridine ring systems with an oxygen atom directly attached in position 4
- C07D475/04—Heterocyclic compounds containing pteridine ring systems with an oxygen atom directly attached in position 4 with a nitrogen atom directly attached in position 2
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J23/00—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00
- B01J23/38—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00 of noble metals
- B01J23/40—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00 of noble metals of the platinum group metals
- B01J23/42—Platinum
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J37/00—Processes, in general, for preparing catalysts; Processes, in general, for activation of catalysts
- B01J37/02—Impregnation, coating or precipitation
- B01J37/0215—Coating
- B01J37/0221—Coating of particles
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Catalysts (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201010505386.3A CN102443006B (zh) | 2010-10-13 | 2010-10-13 | (6r)-四氢生物喋呤盐酸盐的制备方法 |
| CN201010505386.3 | 2010-10-13 | ||
| PCT/CN2010/001836 WO2012048451A1 (zh) | 2010-10-13 | 2010-11-15 | (6r)-四氢生物喋呤盐酸盐的制备方法 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2814018A1 CA2814018A1 (en) | 2012-04-19 |
| CA2814018C true CA2814018C (en) | 2018-11-20 |
Family
ID=45937819
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2814018A Active CA2814018C (en) | 2010-10-13 | 2010-11-15 | Preparation process of (6r)-tetrahydrobiopterin hydrochloride |
Country Status (13)
| Country | Link |
|---|---|
| US (1) | US8895735B2 (zh) |
| EP (1) | EP2628740B1 (zh) |
| JP (1) | JP2013540768A (zh) |
| KR (1) | KR101807904B1 (zh) |
| CN (1) | CN102443006B (zh) |
| AU (1) | AU2010362498B2 (zh) |
| BR (1) | BR112013008720A2 (zh) |
| CA (1) | CA2814018C (zh) |
| DK (1) | DK2628740T3 (zh) |
| ES (1) | ES2550928T3 (zh) |
| MX (1) | MX2013004092A (zh) |
| PL (1) | PL2628740T3 (zh) |
| WO (1) | WO2012048451A1 (zh) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2016189542A1 (en) * | 2015-05-28 | 2016-12-01 | Natco Pharma Ltd | Novel process for the preparation of sapropterin dihydrochloride and its key intermediate, l-biopterin |
| CN112390800B (zh) * | 2019-08-19 | 2022-03-11 | 江苏众强药业有限公司 | L-赤型生物蝶呤类化合物的制备方法 |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS60178887A (ja) * | 1984-02-23 | 1985-09-12 | Kanegafuchi Chem Ind Co Ltd | ５，６，７，８−テトラヒドロ−ｌ−ビオプテリンの製造法 |
| JPS60199889A (ja) | 1984-03-24 | 1985-10-09 | Kanegafuchi Chem Ind Co Ltd | ５，６，７，８−テトラヒドロ−ｌ−エリスロ−ビオプテリンの硫酸塩およびその製法 |
| JPS60204786A (ja) * | 1984-03-29 | 1985-10-16 | Univ Nagoya | （６ｒ）―テトラヒドロビオプテリンの合成法 |
| US4713454A (en) * | 1985-01-28 | 1987-12-15 | Shiratori Pharmaceutical Co., Ltd. | Preparation process of (6R)-tetrahydro-L-biopterin |
| CA2545968C (en) | 2003-11-17 | 2010-03-09 | Merck Eprova Ag | Crystalline forms of (6r)-l-erythro-tetrahydrobiopterin dihydrochloride |
| US7361759B2 (en) | 2004-12-27 | 2008-04-22 | Shiratori Pharmaceutical Co., Ltd | Method for producing L-biopterin |
| MX2010007452A (es) * | 2008-01-07 | 2010-08-18 | Biomarin Pharm Inc | Metodo para sintetizar tetrahidrobiopterin. |
-
2010
- 2010-10-13 CN CN201010505386.3A patent/CN102443006B/zh active Active
- 2010-11-15 AU AU2010362498A patent/AU2010362498B2/en active Active
- 2010-11-15 BR BR112013008720A patent/BR112013008720A2/pt not_active Application Discontinuation
- 2010-11-15 MX MX2013004092A patent/MX2013004092A/es active IP Right Grant
- 2010-11-15 CA CA2814018A patent/CA2814018C/en active Active
- 2010-11-15 US US13/879,285 patent/US8895735B2/en active Active
- 2010-11-15 JP JP2013533065A patent/JP2013540768A/ja active Pending
- 2010-11-15 WO PCT/CN2010/001836 patent/WO2012048451A1/zh active Application Filing
- 2010-11-15 DK DK10858284.2T patent/DK2628740T3/en active
- 2010-11-15 ES ES10858284.2T patent/ES2550928T3/es active Active
- 2010-11-15 PL PL10858284T patent/PL2628740T3/pl unknown
- 2010-11-15 EP EP10858284.2A patent/EP2628740B1/en active Active
- 2010-11-15 KR KR1020137011314A patent/KR101807904B1/ko active IP Right Grant
Also Published As
| Publication number | Publication date |
|---|---|
| CN102443006A (zh) | 2012-05-09 |
| MX2013004092A (es) | 2013-07-05 |
| JP2013540768A (ja) | 2013-11-07 |
| KR20130141505A (ko) | 2013-12-26 |
| EP2628740A4 (en) | 2014-03-19 |
| AU2010362498A1 (en) | 2013-05-09 |
| DK2628740T3 (en) | 2015-10-26 |
| EP2628740B1 (en) | 2015-07-29 |
| BR112013008720A2 (pt) | 2016-06-28 |
| AU2010362498B2 (en) | 2016-04-28 |
| US8895735B2 (en) | 2014-11-25 |
| US20130197222A1 (en) | 2013-08-01 |
| CN102443006B (zh) | 2016-02-24 |
| EP2628740A1 (en) | 2013-08-21 |
| WO2012048451A1 (zh) | 2012-04-19 |
| KR101807904B1 (ko) | 2017-12-11 |
| CA2814018A1 (en) | 2012-04-19 |
| PL2628740T3 (pl) | 2015-12-31 |
| ES2550928T3 (es) | 2015-11-13 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request |
Effective date: 20150831 |